The present invention pertains to the use of lactic acid bacteria capable of adhering to the intestine's mucosa and essentially colonizing it for the prevention of peritonitis. In particular, the present invention relates to the use of such lactic acid bacteria for the prevention of peritonitis associated with liver cirrhosis.
Peritonitis is an inflammation of the peritoneum, attributable to a severe local infection regularly resulting from gastrointestinal inflammation and infection, gastrointestinal perforation and trauma, including surgery or peritoneal dialysis. To this end, pathogenic and potentially pathogenic microorganisms and occasionally cellular debris enter the peritoneum and elicit an immune response by the host, which may often not cope with the challenge of the pathogenic invasion.
This hold true in particular for patients suffering from liver cirrhosis. Cirrhotic patients commonly have intestinal bacterial overgrowth and a decreased immune response, which seems to be at least in part due to an inferior opsonic activity in the ascitic fluid. Advanced cirrhosis is therefore quite often accompanied by a spontaneous bacterial peritonitis (SBP) usually involving gram-negative, enteric pathogens that are normally found in the intestine. Developing SBP in the ascitic fluid is therefore deemed to be caused by bacterial translocation of intestinal bacteria into the peritoneum.
A major jeopardy of peritonitis is bacterial dissemination, i.e., the spread of the pathogens via the blood and lymph systems, resulting in the infection of diverse tissues and leading to a life-threatening situation for the affected individual. Once bacteria have entered the peritoneal cavity, dissemination is quite rapid. Within 6 minutes of intraperitonal inoculation of bacteria in dogs, thoracic lymph has been found culture-positive, while within 12 minutes elevated bacterial levels in the bloodstream may be found.
Although several advances in diagnosis and treatment of peritonitis were made still about one third of hospitalized patients with this infection eventually die from gastrointestinal bleeding, liver failure or the hepatorenal syndrome.
At present the typical medical treatment for the prevention and/or treatment of peritonitis includes antibiotic therapy, especially prior to surgical procedures. This approach suffers, however, from the drawback of developing drug resistant bacteria known to cause peritonitis. Moreover, since both gram-positive and gram-negative microorganisms may cause peritonitis, the use of an antibiotic may not be sufficient in all cases.
In addition, antibiotic treatment is non-specific, also exterminating many non-pathogenic microorganisms that commonly prevent bacterial diseases through bacterial antagonism, in particular in the gastrointestinal tract. Therefore, in applying broad spectrum antibiotics for prolonged periods the growth of most of the bacteria thriving in the intestinal tract is suppressed with the result of antibiotic resistant strains of pathogenic micro-organisms freely propagating. As a consequence, antibiotics may occasionally foster peritonitis, rather than prevent it.
Another approach for the treatment of peritonitis is disclosed in International application WO 97/00081. This document suggests the use of antagonists to CD14, a surface antigen known to interact with lipopolysaccharides of bacterial origin. Bacterially derived lipopolysaccharides are known to be capable to stimulate the immune system by binding to cell surface receptors of cells of the immune system which in turn start to produce and secrete cytokines and other mediators, that stimulate the immune system. However, these cytokines or mediators, respectively, have also been found to be able to support bacterial growth and invasiveness. The gist of the treatment proposed therefore lies in an interruption of the early immune response during which the cytokines/mediators are produced. It is thought that in essentially preventing the production of the cytokines by blocking activation via CD14 the growth of the bacteria is not promoted as well. Yet this method suffers from the drawback that the immune response is essentially impeded as well, so that the host's own defense mechanism is deteriorated.
Consequently, there is a need for an effective method for the prevention and/or treatment of local infections, such as those associated with peritonitis, and this need is satisfied by the present invention.